The association of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α protein expression with clinicopathological characteristics in papillary thyroid carcinoma: A meta-analysis

Objective: To investigate the correlation of hypoxia-inducible factor-1a (HIF-1a) and hypoxia-inducible factor-2a (HIF-2a) protein expression with clinicopathologic characteristics in patients with papillary thyroid carcinoma (PTC) through a meta-analysis.Methods: PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang, and VIP databases were searched from the establishment of the database to February 2023. The New castle-Ottawa Scale was used to evaluate the quality of the literature. Rev Man 5.3 and Stata14.0 were used to conduct a meta-analysis of the included studies.Results: Twenty-eight articles with 2346 samples were included in the Meta-analysis. Compared with normal thyroid tissues, HIF-1a and HIF-2a proteins were highly expressed in PTC tumor tissues. High expression of HIF-1a protein was associated with tumor size (odds ratio [OR] = 4.50, 95% confidence interval [CI]: 2.88-7.04, P < .00001), lymph node metastasis (OR = 4.76, 95% CI: 3.78-5.99, P < .00001), TNM stage (OR = 3.67, 95% CI: 2.68-5.03, P < .00001), capsular invasion (OR = 2.30, 95% CI: 1.43-3.71, P = .0006 < .05), and extrathyroidal extension (OR = 10.96, 95% CI: 4.80-25.02, P < .00001). High expression of HIF-2a protein was associated with lymph node metastasis (OR = 4.18, 95% CI: 2.63-6.65, P < .00001), TNM stage (OR = 2.56, 95% CI: 1.36-4.82, P = .004 < .05), and capsular invasion (OR = 3.84, 95% CI: 1.66-8.88, P = .002 < .05). In addition, we concluded for the first time that there was a statistically significant difference in the expression of HIF-1a and HIF-2a in PTC patients (OR = 2.36, 95% CI: 1.26-4.42, P = .007 < .05).Conclusions: The high expression of HIF-1a and HIF-2a proteins is closely related to some clinicopathological parameters of PTC, and can provide potential biological indicators for the diagnosis and prognosis of PTC.